Reconstrucción craneal con implante personalizado / Cranial reconstruction with a custom-made implant

Objetivo: Este artículo describe el uso de un implante hecho a la medida para la reconstrucción de un defecto craneal. Caso clínico: Un paciente con defecto craneal producto de traumatismo craneoencefálico. Se utilizó un implante a medida del paciente de polieteretercetona (PEEK Optima-LT, Synthes). Resultados: No hubo necesidad de ajuste transquirúrgico del implante, ni se presentaron reacciones de rechazo, infección o exposición del implante en el periodo posoperatorio (3 meses de seguimiento). El paciente disminuyó la sintomatología reportada previa a la reconstrucción, y la mejoría del contorno craneal fue notoria. Conclusión: Los implantes hechos a medida se presentan como un método razonable para la reconstrucción de defectos craneales graves. Deben evaluarse diversos factores, tales como el costo, el procedimiento quirúrgico y los resultados a largo plazo(AU)

Purpose: This article describes the use of a custom-made implant for cranial reconstruction. Clinical case: In a patient with a traumatic cranial defect, a custom-made implant of Polyetheretherketone (PEEK Optima-LT, Synthes) was used for reconstruction. Results: Intraoperative implant adjustments were not required. No rejection reactions, infections or implant exposure occurred in the postoperative period (3 months follow-up). The patient's preoperative symptoms diminished and the cranial contour improved notably. Conclusion: Custom-made implants are proposed as a feasible method for the reconstruction of severe skull defects. Factors such as cost, surgical procedure, and long-term results, must be evaluated(AU)

Coexistence of two different pseudohypoparathyroidism subtypes (Ia and Ib) in the same kindred with independent Gs{alpha} coding mutations and GNAS imprinting defects.

BACKGROUND: Pseudohypoparathyroidism (PHP) defines a rare group of disorders whose common feature is resistance to the parathyroid hormone. Patients with PHP-Ia display additional hormone resistance, Albright hereditary osteodystrophy (AHO) and reduced Gsalpha activity in easily accessible cells. This form of PHP is associated with heterozygous inactivating mutations in Gsalpha-coding exons of GNAS, an imprinted gene locus on chromosome 20q13.3. Patients with PHP-Ib typically have isolated parathyroid hormone resistance, lack AHO features and demonstrate normal erythrocyte Gsalpha activity. Instead of coding Gsalpha mutations, patients with PHP-Ib display imprinting defects of GNAS, caused, at least in some cases, by genetic mutations within or nearby this gene. PATIENTS: Two unrelated PHP families, each of which includes at least one patient with a Gsalpha coding mutation and another with GNAS loss of imprinting, are reported here. RESULTS: One of the patients with GNAS imprinting defects has paternal uniparental isodisomy of chromosome 20q, explaining the observed imprinting abnormalities. The identified Gsalpha coding mutations include a tetranucleotide deletion in exon 7, which is frequently found in PHP-Ia, and a novel single nucleotide change at the acceptor splice junction of intron 11. CONCLUSIONS: These molecular data reveal an interesting mixture, in the same family, of both genetic and epigenetic mutations of the same gene.

Gene polymorphisms in TYMS, MTHFR, p53 and MDR1 as risk factors for breast cancer: a case-control study.

Breast cancer (BC) is a complex disease influenced by environmental and genetic factors. The disease has important genetic and environmental components, most of them are still unknown. An important role of gene polymorphisms related to the risk of developing BC has been reported. However, the results have been controversial. We investigated the association of TSER, MTHFR C677T, p53 codon 72 and MDR1 C3435T gene polymorphisms with breast carcinoma in women from Canary Islands (Spain). Blood samples collected from 135 patients with BC and 304 healthy controls all of them Caucasian, were analyzed through polymerase chain reaction-restriction fragment length polymorphism. Subsequently, a structured questionnaire including patient history and risk factors in relation to BC development was filled out. Allelic frequencies of these genetic variations were: TSER, (2) 0.55 and (3) 0.45 in cases, 0.49 and 0.51 respectively in controls (P=0.240); MTHFR C677T, (C) 0.63 and (T) 0.37 in cases, 0.60 and 0.40 respectively in controls (P=0.568); p53 Arg72Pro, (Arg) 0.74 and (Pro) 0.26 in cases and controls (P=0.910); MDR1 C3435T, (C) 0.52 and (T) 0.48 in cases, 0.55 and 0.45 respectively in controls (P=0.523). We did not observe any gene polymorphism as a risk factor to develop BC. A statistical association was observed between p53 codon 72 polymorphism and family history of breast cancer in both groups, as well as between MDR1 C3435T and smoking habits in cases (P<0.05). Gene polymorphisms vary by regions. The present study contributes to the characterization of the genetic pattern of the Canary population.

Discriminant function analysis as decision support system for the diagnosis of acute leukemia with a minimal four color screening panel and multiparameter flow cytometry immunophenotyping.

Despite several recommendations for standardization of multiparameter flow cytometry (MFC) the number, specificity and combinations of reagents used by diagnostic laboratories for the diagnosis and classification of acute leukemias (AL) are still very diverse. Furthermore, the current diagnostic interpretation of flow cytometry readouts is influenced arbitrarily by individual experience and knowledge. We determined the potential value of a minimal four-color combination panel of 13 monoclonal antibodies (mAbs) with a CD45/sideward light scatter-gating strategy for a standardized MFC immunophenotyping of the clinically most relevant subgroups of AL. Bone marrow samples from 155 patients with acute myeloid leukemia (AML, n=79), B-cell precursor acute lymphoblastic leukemia (BCP-ALL, n=29), T-cell precursor acute lymphoblastic leukemia (T-ALL, n=12) and normal bone marrow donors (NBMD, n=35) were analyzed. A knowledge-based learning algorithm was generated by comparing the results of the minimal panel with the actual diagnosis, using discriminative function analysis. Correct classification of the test sample according to lineage, that is, BCP-ALL, T-ALL, AML and differentiation of NBMD was achieved in 97.2% of all cases with only six of the originally applied 13 mAbs of the panel. This provides evidence that discriminant function analysis can be utilized as a decision support system for interpretation of flow cytometry readouts.

Quantitative analysis of bcl-2 expression in normal and leukemic human B-cell differentiation.

Lack of apoptosis has been linked to prolonged survival of malignant B cells expressing bcl-2. The aim of the present study was to analyze the amount of bcl-2 protein expressed along normal human B-cell maturation and to establish the frequency of aberrant bcl-2 expression in B-cell malignancies. In normal bone marrow (n=11), bcl-2 expression obtained by quantitative multiparametric flow cytometry was highly variable: very low in both CD34(+) and CD34(-) B-cell precursors, high in mature B-lymphocytes and very high in plasma cells. Bcl-2 expression of mature B-lymphocytes from peripheral blood (n=10), spleen (n=8) and lymph node (n=5) was significantly higher (P<0.02) in CD23(-) as compared to CD23(+) B cells, independent of the type of tissue analyzed. Upon comparison with normal human B-cell maturation, bcl-2 expression in neoplastic B cells from 144 patients was found to be aberrant in 66% of the cases, usually corresponding to bcl-2 overexpression (63%). Follicular lymphoma (FL) carrying t(14;18) and MALT lymphoma were the only diagnostic groups constantly showing overexpression of bcl-2. Bcl-2 overexpression was also frequently found in precursor B-acute lymphoblastic leukemia (84%), typical (77%) and atypical (75%) B-cell chronic lymphocytic leukemia, prolymphocytic leukemia (two of three cases), mantle cell lymphoma (55%), but not in t(14;18)(-) FL, splenic marginal zone lymphoma, Burkitt lymphoma and multiple myeloma.

Comparative analysis of the morphological, cytochemical, immunophenotypical, and functional characteristics of normal human peripheral blood lineage(-)/CD16(+)/HLA-DR(+)/CD14(-/lo) cells, CD14(+) monocytes, and CD16(-) dendritic cells.

Human peripheral blood (PB) CD14(lo)/HLA-DR(+) cells were initially described as a subset of mature monocytes. Recently, it has been suggested that these represent a part of a new subset of dendritic cells (DC), characterized by the coexpression of MDC-8/HLA-DR/CD16. The aim of the present paper was to analyze the morphological, cytochemical, phenotypical, and functional characteristics of PB CD16(+)/HLA-DR(+) cells compared to both PB CD14(+) monocytes and CD16(-) DC. In contrast to CD14(+) monocytes, purified CD16(+)/HLA-DR(+) cells displayed cytoplasmic veils and lacked cytoplasmic myeloperoxidase and alpha-naphthyl acetate esterase. Normal human PB CD16(+)/HLA-DR(+) cells also displayed phenotypic characteristics different from those of CD14(+) monocytes: they lacked the CD64 Fcgamma receptor, showed lower levels of CD32, and expressed higher amounts of CD16 compared to CD14(+) monocytes. They also displayed a different pattern of expression of other antigens, including CD14, HLA-DR, CD45RA, CD45RO, complement receptors and complement regulatory surface proteins, adhesion and costimulatory molecules, and cytokine receptors, among others. When compared to CD16(-) DC, CD16(+)/HLA-DR(+) cells showed reactivity for CD16, dim positivity for CD14, higher expression of both Ig- and complement-receptors and lower reactivity for HLA-DR, adhesion, and costimulatory molecules (with the exception of CD86). The CD16(+)/HLA-DR(+) cell subset displayed a higher Ig/complement-mediated phagocytic/oxidative activity than CD16(-) DC, although this activity was significantly lower than that of mature monocytes. Regarding cytokine production at the single cell level, LPS plus IFN-gamma-stimulated PB CD16(+)/HLA-DR(+) cells produced significant amounts of IL1beta, IL6, IL12, TNFalpha, and IL8; however, the percentage of cytokine-producing cells and the amount of cytokine/cell were lower in CD16(+)/HLA-DR(+) cells than in CD14(+) monocytes. In addition, upon comparing CD16(+)/HLA-DR(+) cells with CD33(+++)/CD16(-) DC, we found that the percentage of cytokine-producing cells and the amount of cytokine/cell were significantly different in both cell subsets. In summary, our results show that CD16(+)/HLA-DR(+) cells clearly display different morphologic, cytochemical, immunophenotypical, and functional characteristics compared to both mature monocytes and CD16(-) DC. Interestingly, these cells are more frequent than other DC in normal human adult PB and cord blood samples, while they are less represented in normal bone marrow.

Leuprolide suppression of androgen secretion by hilus cell hyperplasia within the wall of an ovarian cyst.

Androgenic manifestations coexisting with hilus cell hyperplasia adjacent to a tumour or an ovarian cyst are extremely rare. We report the case of a post-menopausal woman with hirsutism associated with hilus cell hyperplasia within the wall of an ovarian cyst. The pattern of steroid secretion revealed increased testosterone release. Suppression of testosterone to 'normal range' was seen in response to leuprolide administration. This new approach demonstrates gonadotrophin dependence of hilus cell hyperplasia within an ovarian cyst.